Method and system for analyzing drug adverse effects

ABSTRACT

The system of the present invention for assessing and analyzing the risks of adverse effects resulting from the use of at least one substance of interest, comprises a selector for identifying at least one substance of interest; a profiler for selecting from multiple profiles related to the safety of the at least one substance of interest, using at least one filter; at least one data mining engine; and an output device for displaying the analytic results from the data mining engine. Preferably, the at least one data mining engine is selected from (1) a proportional analysis engine to assess deviations in a set of the reactions to the drug of interest; (2) a comparator to measure the reactions to the drug of interest against a user-defined backdrop, and (3) a correlator to look for correlated signal characteristics in drug/reaction/demographic information; and an output device whereby a user can receive analytic results from the selector, the proportional analysis engine, the comparator, and the correlator.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a continuation application of U.S. Ser. No.09/681,585, filed May 2, 2001, now U.S. Pat. No. ______, issued ______,the entirety of which is incorporated herein by reference.

BACKGROUND OF INVENTION

1. Field of the Invention

The present invention relates to a system and method for assessing andanalyzing the risks of adverse effects resulting from the use of aparticular drug, either alone or in combination with other drugs,nutrients, supplements, and other substances.

2. Description of the Related Art

In September 1997, information regarding cardiopulmonary disease relatedto the use of fenfluramine and phentermine (“fen-phen”) prompted theUnited States Food and Drug Administration (FDA) to request themanufacturers of these drugs to voluntarily withdraw both treatments forobesity from the market. Subsequent studies show a 25 percent incidenceof heart valve disease apparently resulting from diet drug use. Thus, upto 1,250,000 people may have sustained heart valve damage from thesediet drugs and the FDA indicates that this may be the largest adversedrug effect the agency has ever dealt with.

Current estimates are that some 2.2 million hospital patients hadserious adverse drug reactions and more than 100,000 people die eachyear from adverse reactions to prescription drugs. Accordingly, federalofficials have recommended that the FDA require hospitals to report allserious drug reactions to the agency. The Inspector General of theDepartment of Health and Human Services has also indicated that the FDAshould also work to identify harmful effects of new drugs and encouragehealth-care providers to rapidly call the FDA with information aboutdrug side effects. As new drugs are introduced at increasing rates, theFDA will likely need additional resources to protect the public fromhazardous drug side effects:

If one or two adverse drug reactions slip through the FDA's reportingprocess, the results can be tragic for some patients. That is especiallytrue when the adverse reactions are rare but serious—such as in the caseof liver failure caused by medication. All drugs have the potential toharm or kill the people they are designed to help. An injection ofpenicillin can kill in minutes if the recipient is allergic to thislife-saving drug. Even common aspirin can be deadly.

Clinical trials of a new drug often involve a few hundred patients andtherefore may not reveal that a drug can cause serious injury or deathin one patient in 10,000 or even 1,000 patients. Accordingly, it iscritical for researchers and drug companies to be able to analyze andpredict adverse reactions among patients in their studies.

In addition, in clinical trials for drugs used to treat diseases such asdiabetes, which affects so many people and is difficult to treat, FDAofficials often face tremendous pressure to accelerate their approvalprocess. Often, in this “fast-track” process, cases of adverse drugeffects may slip through reporting procedures.

An even bigger challenge to the FDA is the occurrence of adverse drugreactions after the drug is on the market. In this case the drug isprescribed to a much larger population of patients, many of whom aretaking other substances such as extracts, nutrients, vitamins, hormonesor drugs that might have an adverse effect with the prescribed drug.

Thus, there is a need for effective analysis of adverse drug effects.Unfortunately, such a system has not been available.

U.S. Pat. No. 5,758,095 to Albaum et al., “Interactive MedicationOrdering System,” discloses a system and method for ordering andprescribing drugs for a patient. This system includes an improvedprocess for facilitating and automating the process of drug order entry.The user may interact with the system in a variety of ways such askeyboard, mouse, pen-base entry or voice entry. The system includes adatabase containing medical prescribing and drug information which isboth general and patient-specific. The system also permits the user toview current and previously prescribed medications for any patient. Thesystem can alert the user to potentially adverse situations as a resultof the prescribed medication based on information in the database.

U.S. Pat. No. 5,299,121 to Brill et al., “Non-Prescription DrugMedication Screening System,” discloses a system for use in pharmacieswhich uses customer inputs to assist the customer with the selection ofan appropriate non-prescription medication to relieve symptoms of anillness, injury or the like. The system uses an expert system to performthe selection. The system utilizes a personal computer with a keyboard,monitor and disk drive as input/output devices with appropriateprogramming for prompting a user to input information which is used by aknowledgebase to determine non-prescription medications which may bepurchased by the customer to relieve symptoms of injuries and illnessesincluded in the knowledgebase.

U.S. Pat. No. 5,594,637 to Eisenberg et al., “System And Method ForAssessing Medical Risk,” discloses a system and method for assessing themedical risk of a given outcome for a patient comprising obtaining testdata from a given patient corresponding to at least one test marker forpredicting the medical risk of a given outcome and obtaining at leastone variable relating to the given patient and transforming the testdata with the variable to produce transformed data for each testmarkers. A database of transformed data from previously assessedpatients is provided, and mean and standard deviation values aredetermined from the database in accordance with the actual occurrence ofthe given outcome for previously assessed patients. The transformed datais compared with the mean and standard deviation values to assess thelikelihood of the given outcome for the given patient and the databaseis updated with the actual occurrence for the given patient, whereby thedetermined mean and standard deviation will be adjusted.

U.S. Pat. No. 6,067,524 to Byerly et al., “Method And System ForAutomatically Generating Advisory Information For Pharmacy PatientsAlong With Normally Transmitted Data,” discloses a method and system forgenerating advisory messages to pharmacy patients, including appendingpatient-specific information to a data record containing normallytransmitted information. The data record is transmitted between a thirdparty computer and a pharmacy computer during a pharmacy transaction.The data record transmitted to the pharmacy computer is captured by anadvisory computer as the data record is received by the pharmacycomputer or after the data record is transmitted to the pharmacycomputer, and the patient-specific information is extracted from thecaptured data record. The advisory computer generates an advisorymessage based on the extracted patient-specific information, and ittransmits the generated advisory message to a pharmacy printer.

U.S. Pat. No. 6,000,828 to Leet, “Method Of Improving Drug Treatment,”discloses a computer implemented method and system for improving drugtreatment of patients in local communities by providing drug treatmentprotocols for particular disease states, such as Diagnosis Related Group(DRG) classifications. The protocol contains ranked recommendations fordrug treatments of the disease state, and the computer system collectsinformation about the risks and benefits of the drug treatments. Theinformation collected about the treatments is used to modify therankings of the drug treatments in the protocol.

U.S. Pat. No. 6,219,674 to Classen, “System for creating and managingproprietary product data” discloses systems and methods for creating andusing product data to enhance the safety of a medical or non-medicalproduct. The systems receive vast amounts of data regarding adverseevents associated with a particular product and analyze the data inlight of already known adverse events associated with the product. Thesystem develops at least one proprietary database of newly discoveredadverse event information and new uses for the product and may catalogadverse event information for a large number of population sub-groups.The system may also be programmed to incorporate the information intointellectual property and contract documents. Manufacturers can includethe information in consumer product information that they provide toconsumers or, in the case of certain medical products, prescribers ofthe medical products.

However, none of these references provides a system and method foranalyzing the risks of adverse effects resulting from the use of aparticular drug, either alone or in combination with other substancesincluding but not limited to hormones, drugs, nutrients, andsupplements.

Thus, there remains a need for a more efficient and effective system andmethod for analyzing the risks of adverse effects resulting from the useof a particular drug, either alone or in combination with othersubstances including bit not limited to hormones, drugs, nutrients, andsupplements. There also remains a need for a more efficient andeffective system and method for analyzing the risks of adverse effectsresulting from the use of a particular drug on particular segments ofthe population.

SUMMARY OF INVENTION

The system of the present invention for assessing and analyzing therisks of adverse effects resulting from the use of at least onesubstance of interest, comprises a selector for identifying at least onesubstance of interest; a profiler for selecting from multiple profilesrelated to the safety of the at least one substance of interest, usingat least one filter; at least one data mining engine; and an outputdevice for displaying the analytic results from the data mining engine.

The system of the present invention is also a system for assessing andanalyzing the risks of adverse effects resulting from the use of atleast one drug of interest, comprising: a selector for identifying atleast one drug of interest; a profiler for selecting from multipleprofiles related to the safety of the at least one drug of interest,using at least one filter; at least one data mining engine; and anoutput device for displaying the analytic results from the data miningengine.

The method of the present invention for assessing and analyzing therisks of adverse effects resulting from the use of at least onesubstance of interest comprises identifying the at least one substanceof interest; selecting the profile of the at least one substance ofinterest related to the safety of the at least one substance ofinterest, using at least one filter; analyzing the risks of adverseeffects resulting from the use of the at least one substance of interestusing at least one data mining engine; and displaying the results of theanalysis of risks of adverse effects resulting from the use of the atleast one substance of interest.

The method of the present invention for assessing and analyzing therisks of adverse effects resulting from the use of at least one drug ofinterest also comprises identifying the at least one drug of interest,as well any other drugs, nutrients, supplements, and other substances;selecting the profile of the at least one drug of interest related tothe safety of the at least one drug of interest, using at least onefilter; analyzing the risks of adverse effects resulting from the use ofthe at least one drug of interest using at least one data mining engine;and displaying the results of the analysis of risks of adverse effectsresulting from the use of the at least one drug of interest.

Preferably, the system and method of the present invention for assessingand analyzing the risks of adverse effects resulting from the use of adrug of interest, either alone or in combination with other drugs,nutrients, supplements, and other substances comprises at least one datamining engine preferably selected from the group consisting of (1) aproportional analysis engine to assess deviations in a set of thereactions to the drug of interest, (2) a comparator to measure thereactions to the drug of interest against a user-defined backdrop, and(3) a correlator to look for correlated signal characteristics indrug/reaction/demographic information; and an output device whereby auser can receive analytic results from the selector, and the at leastone data mining engine.

The present invention also provides a system and method for assessingthe relationships between any and all dimensions, in any and allcombinations, in assessing and analyzing the risks of adverse effectsresulting from the use of one or more particular drugs. For example, thedimensions can be analyzed in combinations of two dimensions, incombinations of three dimensions, and others combinations, as well. As aspecific example, the present invention permits a view of a drugreaction (for example, rash) across all drugs. The present inventionalso permits analysis of the association between outcomes (for example,hospitalization) and other dimensions (for example, age, gender,concomitant drug, reaction, among others).

It will appreciated that such a system and method for assessing andanalyzing the risks of adverse effects resulting from the use of one ormore particular drugs is advantageous to the various risk assessors whoare tasked with making such determinations. Such risk assessors includegovernmental agents who perform such assessment for regulatory purposes,as well as agents of pharmaceutical manufacturers who are tasked withsuch assessments.

The present invention, which provides a system and method for assessingand analyzing the risks of adverse effects resulting from the use of oneor more particular drugs, offers an enhanced degree of analysis notpreviously available. This enhanced degree of analysis permits theidentification of associations and, thus, potential causal elementsregarding adverse effects resulting from the use of one or moreparticular drugs.

The present invention provides answers to several key questions that areessential to public health. For example, various safety groups, bothgovernment and private, are charged with monitoring the post-marketbehavior of drugs and determining “signals” that indicate a relationshipamong adverse reactions, demographics, and other elements such asoutcomes. Unexpected or previously unrecognized adverse drug effects cantake the forms of single reactions, groups of reactions, or increases ina labeled reaction. Such adverse drug effects might be due to the higherexposure to the general population experienced in post-market therapy orsuch effects can be a reaction that has a demographic (genetic orotherwise) emphasis in an age or gender group.

Further, with efficient and effective analysis of adverse drug effects,pharmaceutical research and development professionals can learn moredetails of the reaction profiles of drugs and the at-risk populationswho may be prescribed those drugs. This information would allow a moreeffective selection of lead compounds and would produce drugs with lessrisk of adverse effects.

Thus, the present invention allows for analysis of adverse drug effectswith enhanced speed and flexibility. The present invention also offersnew insights with regard to adverse drug effects and augments theexisting processes of drug development.

Accordingly, it is an object of the present invention to provide a moreefficient and effective system and method for analyzing the risks ofadverse effects resulting from the use of a drug, either alone or incombination with other drugs, nutrients, supplements, and othersubstances.

It is an object of the present invention to provide a more efficient andeffective system and method for analyzing the risks of adverse effectsresulting from the use of a drug.

It is further an object of the present invention to provide a moreefficient and effective system and method for analyzing the risks ofadverse effects resulting from the use of a drug in combination withanother substance.

Yet another object of the present invention is to provide a moreefficient and effective system and method for analyzing the risks ofadverse effects resulting from the use of a drug in combination withanother substance, wherein the substance is a nutrient, vitamin,hormone, or drug.

An advantage of the present invention is that potential adverse effectsto the health of a human or animal may be predicted and avoided.

Yet another object of the present invention is to provide a moreefficient and effective system and method useful for analyzing the risksof adverse effects resulting from the use of a drug, alone or incombination with another substance, wherein the substance is a nutrient,vitamin, hormone, or drug, further wherein the system and method can beused by providers of medical or veterinary care services.

Another object of the present invention is to provide a more efficientand effective system and method useful for analyzing the risks ofadverse effects resulting from the use of a drug, alone or incombination with another substance, wherein the substance is a nutrient,vitamin, hormone, or drug, further wherein the system and method can beused by consumers of medical care services.

A greater understanding of the present invention and its concomitantadvantages will be obtained by referring to the following figures anddetailed description provided below.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is chart indicating the page flow of the present invention;

FIG. 2 is an overview of the present invention;

FIG. 3 is a depiction of a home page of the present invention;

FIG. 4 is a representation of a filter selection page of the presentinvention;

FIG. 5 is a representation of a selector page of the present invention;

FIG. 6 is an illustration of an exemplary pedigree screen of the presentinvention;

FIG. 7 is a depiction of an exemplary reactions table in the profilercomponent of the present invention;

FIG. 8 is a representation of a concomitant drugs table in the profilercomponent of the present invention;

FIG. 9 is a depiction of a demographics table in the profiler componentof the present invention;

FIG. 10 is an illustration of a report dates table in the profilercomponent of the present invention;

FIG. 11 is a representation of an outcomes table in the profilercomponent of the present invention;

FIG. 12 is a depiction of a reaction filter screen of the presentinvention;

FIG. 13 is an illustration of a correlation results screen of thepresent invention;

FIG. 14 is a representation of a correlation details screen of thepresent invention;

FIG. 15 is a depiction of a case details screen of the presentinvention;

FIG. 16 is an exemplary illustration of a radar screen display of thepresent invention;

FIG. 17 is an illustration of a proportional analysis selection screenof the present invention;

FIG. 18 is a representation of a proportional analysis results screen ofthe present invention;

FIG. 19 is a depiction of a tabular version of a proportional analysisscreen of the present invention;

FIG. 20 is an illustration of a comparator screen of the presentinvention; and

FIG. 21 is a representation of a case list of the present invention.

DETAILED DESCRIPTION

The present invention provides a system and method for assessing andanalyzing the risks of adverse effects resulting from the use of one ormore particular drugs, either alone or in combination with other drugs,nutrients, supplements, vitamins, foods, beverages, and othersubstances.

The primary components of a preferred embodiment of the present systemand method for analysis of adverse drug effects are a combination of thefollowing: one or more integrated databases; a selector for selecting atleast one drug for analysis (based on the generic, brand names ortherapeutic category); a profiler for displaying statistics thatdescribe behavior for the drug in multiple dimensions; a series of atleast two filters and the means to control the at least two filtersindividually and in combination; at least one of three or more datamining engines selected from the group of a correlator, a proportionalanalysis engine, and a comparator; and a graphical user interface fordisplaying the results of the analysis.

For purposes of the present invention, a substance shall be understoodto include one or more elements of the set of drugs, foodstuffs,beverages, nutrients, vitamins, toxins, chemicals, hormones, andsupplements.

A preferred page flow of the present invention is indicated in FIG. 1.Box 100 represents a user login window. If the user successfully logs inand is authenticated, then the user is then placed in the home page 101of the present invention. From the home page 101, the user can add auser at the Add a User Box 102; download an data image at the ImageViewCorrelation Viewer Box 103; review a previously created filter at theFilter Contents Pop-up Box 104; review a previously submittedcorrelation task at the Correlated Terms Line Listing Box 105; launch aproportional analysis task at the Proportional Analysis Results Page Box108; or query the system with regard to a drug at Drug Selector Page Box111. It will be appreciated that the user can query regarding a drug bygeneric name, trade name, or therapeutic category.

Preferably, if the user is reviewing a previously submitted correlationtask at the Correlated Terms Line Listing Box 105, then the presentinvention permits the user to access the case list at the Case List Box106 and, further, permits the user to drill down on individual elementsin the case list and obtain case details at the Case Details Box 107.

Preferably, if the user is launching a proportional analysis task at the

Proportional Analysis Results Page Box 108, then the present inventionpermits the user to access the case list at the Case List Box 109 and,further, permits the user to drill down on individual elements in thecase list and obtain case details at the Case Details Box 110.

Preferable, if the user is querying the system with regard to a drug atDrug Selector Page Box 111, then the present invention permits the userto access the drug profile at the Profile Page Box 112, further, permitsthe user to access the case list at the Case List Box 113 and, stillfurther, permits the user to drill down on individual elements in thecase list and obtain case details at the Case Details Box 114.

From the Profile Page Box 112, the user preferably can either accessmore details regarding the various dimensions of the risk assessment atthe More Details Box 115 or filter in various dimensions of the riskassessment at the Filter in Various Dimensions Box 121.

If the user has chosen to access more details, then the user ispreferably presented with multiple dimensions of the risk assessmentfrom which to access more information. Preferred dimensions of riskassessment include, but are not limited to, Reactions More Details Box116, Concomitant Drugs More Details Box 117, Demographics More DetailsBox 118, Report Dates More Details Box 119, and Outcomes More DetailsBox 120.

Preferably, if the user has chosen to filter in various dimensions ofrisk assessment, then the user is preferably presented with multiplefilters for the dimensions of the risk assessment. Preferred filters ofdimensions of risk assessment include, but are not limited to, ReactionsFilters Box 122, Concomitant Drugs Filters Box 123, Demographics FiltersBox 124, Report Dates Filters Box 125, and Outcomes Filters Box 126.

The preferred components of the present invention are illustrated inFIG. 2, which provides an overview of the system and method of thepresent invention. The user preferably accesses the system of thepresent invention by means of Home Page 200. From Home Page 200 the usercan proceed to the Selector 201, where the user can select a drug foranalysis. Having selected the drug of interest, the user can thenpreferably proceed to the Profiler 202, which preferably displaysstatistics that describe the behavior of the drug of interest. From theProfiler 202 the user can then preferably proceed to employ one or moreFilters 203, which permit recalculation of the statistics by selectingamong the available variables. Once a set of cases is determined, forexample, by the use of one or more filters, the cases can thenpreferably be submitted to at least one of three or more Data MiningEngines 204. The output form the data mining of formats, including, butnot limited to a sortable table, a sortable line listing, and a radarscreen, thus, allowing rapid identification of signals and providing theuser the ability to drill down to individual case details.

Alternatively, in another preferred embodiment, from Home Page 200 theuser can choose a profile from the Profiler 202, apply one or moreFilters 203, process the set of cases using the Data Mining Engines 204and display the results with the Viewer 205.

Preferably, the present invention operates on at least one of twointegrated databases: an external public database characterized bybreadth of data across all drugs and a database containing internal dataof an organization or an individual characterized by increased detailwith regard to one or more specific groups of drugs. It will beappreciated that a database containing the internal data of anindividual can refer to a number of different situations, including butnot limited to the biological/medical/genetic/drug sensitivity of anindividual.

In both cases, the source and purpose of the data may vary, includingpost-marketing surveillance, clinical trial data, health care systemdata, research databases, and literature, among others.

The public database preferably is at least one database selected fromeither a combination of one or more of the FDA's Spontaneous ReportingSystem (SRS)(after to November 1997)) and the FDA's Adverse EventReporting System (AERS)(after to November 1997)), the World HealthOrganization adverse event database, or other country-specificregulatory or epidemiological databases, such as the UK Advert systemand the General Practice Research Database (GPRD). These publicdatabases are updated regularly as they release new case data. In arelated invention, which is a particularly preferred embodiment of thepresent invention, the present system and method for analyzing adversedrug effects relies upon a derivative of these public databases that hascleaned, parsed in to a relational database, and mapped to knowndictionaries, and standardized for efficient searching and querydefining. This preferred derivative database has over 2 million casesrepresenting 30 years of adverse events as reported to regulatoryauthorities. Additionally, the derivative database links the adverseevent (AE) case data to Medical Dictionary for Regulatory Activities(MedDRA), Coding Symbols for a Thesaurus of Adverse Reaction Terms(COSTART), and World Health Organization (WHO) Adverse Drug ReactionTerminology (WHOART), among others for reactions, and the National DrugCode Directory (NCDC), Orange Book or WHO Drug dictionaries for drugs.The invention includes the facility to substitute and manage standarddictionaries, both public and private, for all dimensions.

In a preferred embodiment, the present system and method also operate ona database containing internal data of an organization. For example,such an internal database could be the proprietary database of apharmaceutical company or the contemporaneous database of a clinicalinvestigator during the course of clinical trials upon a drug.

It will be appreciated that one preferred embodiment of the presentinvention utilizes a log-on screen. In one preferred embodiment, accessto the present invention is provided by means of the Web. In anotherpreferred embodiment, access to the invention is provided by means of aclient/server interface. The present system and method preferablysupports all browsers including Netscape and Internet Explorer foraccess. In a particularly preferred embodiment, different URLs are usedfor the public database and for the internal database. This allowsoperating in two databases concurrently if two instances of the Webbrowser are opened. It also allows virtually unlimited simultaneousprocesses, and simultaneous processing at various locations.

The use of multiple sessions also enable a range of comparisons, in eachand every dimension. The “differencing engine” or comparator providesimmediate information on similarities and differences.

In another preferred embodiment of the present invention, a home screenis used to launch searches, and review results of the analytical enginesand prior work. For example, from the home screen a user can (1) selecta drug to study by either name or by therapeutic category, (2) recall apreviously saved filter (that was created, named and saved previously,(3) review previously submitted analyses, or (4) invoke certain datamining engines directly. An exemplary version of a home page of thepresent invention is provided in FIG. 3. From this home screen, the usercan use field 301 to select a drug to study by generic name, trade name,or therapeutic category. The user can also use field 302 to recall apreviously saved query (called a filter). Further, the user can usefield 303 to recall previously submitted analyses. Additionally, theuser can use field 304 to invoke the proportional analysis engine.

The home page is preferably the user's command center for analysis. Thehome page is preferably always accessible from any other screen.

Preferably, the home screen has four areas. The first area is a link tothe selector, thus, allowing a user to easily reach the drug selectionscreen through any level of detail on a drug. The second is a filterarea. The user can view and apply previously saved filters. The thirdsection is the data mining engine section which allows a user to invokeone or more of the data mining engines. The fourth area permits the userto review previously generated analyses.

With regard to the selection of a drug, this feature allows a user toselect at least one drug to study and to search for information on thatat least one drug by using either its generic name, its trade name, itstherapeutic category, or its chemical name. In addition, the inventionprovides the ability to develop specific other valuable taxonomies, suchas a “super generic” including all salts of a drug, or a sub-brand, forexample distinguishing between a once a day version of a drug from aonce a week version of the drug.

Concerning selecting a previously saved query, this feature (referred toas a filter) is a preferred paradigm to reduce the routine of inputtinga previously employed and saved query. By establishing parameters forsearching, a user does not need to define ad hoc queries. Knowledge ofthe pharmacovigilance domain is used to present users withfilter/query-building interfaces that are more in line with the thoughtprocesses and paradigms employed by such users. A user can preserve theset of parameters of a query (a filter) each time he/she refines aprofile, and further, a user can employ a filter he/she has developed ina previous search the next time he/she wishes to view the same or anupdated set of cases.

It will be appreciated that one aspect of the present invention is thatthe combination of profiles and filters allows a user to employcontinuous drill-down and hypothesis testing in real time so as toassess and analyze risk. It will further be appreciated that the presentinvention, by permitting a user to quickly switch on and off theelements of a filter using context-sensitive tables provides an enhancedsystem and method for assessing and analyzing risk in real time.Examples of the use of such “quick” filters are selecting and/ordeselecting the “Designated Medical Events” as defined by the FDA;selecting and/or deselecting labeled adverse effects; selecting and/ordeselecting groups of reactions that represent a syndrome.

For example, FIG. 4 provides a representation of a preferred filterscreen. Various preferred fields of a filter screen are presented,including, but not limited to, Reactions (field 400), Concomitant Drugs(field 401), Demographics (field 402), Report Dates (field 403), andOutcomes (field 404).

In invoking a saved filter, a user is offered the option of viewing orapplying (querying with) a saved filter, and a pull-down menu allows auser to select one of the filters previously created and saved. Pushingthe “View” button allows a review of the specific details of the filter.In the example provided, a user had created and saved a filter he/shehad labeled “Filter 2” for a search on Candesartan Cilexetil. The searchresults show the drug's Reactions, including its MedDRA Hierarchy Group(System-Organ-Class (SOCs), etc.), and a pull-down menu showing thespecific reactions (ear and labyrinth disorders, for example) includedin the filter.

Case sets, as well as drug sets, can be created, named, and savedsimilar to filters. Because these case sets generate a list rather thana logic description, viewing and changing are performed with a listmanager. Filters, drug sets, and case sets can all be combined or mergedto provide a rich set of functions, and great flexibility.

The preferred parameters of a filter include reactions (listed as“included” or “off”); concomitant drugs (listed or “off”); demographics(listed as per previously set brackets or “off”); report dates (listedor “off”); and outcomes (listed or “off”). If a user wishes to applythis saved filter as his/her current query, he/she would click on the“Apply” button. At this point, a user would be taken to the profilescreens for that drug and that set of filters.

The present invention allows for flexible addition of dimensions. Forexample, if genotype or racial background were added as a dimension, thepresent invention would display, control and analyze this dimension,along with the other dimensions of issue.

With regard to the review of the previous analysis aspect of the presentinvention, this section of the home page provides information onprevious analyses a user has run using the correlator engine of thepresent invention. As illustrated in FIG. 3, the correlator enginenotices provide information on analyses that have been previouslycompleted including date and time, task number, and generic drug. Eachlisting ends with a hyperlink that a user can employ to view the resultsof the search. A “delete” function is preferably provided to manage thislist.

Concerning the proportional analyzer aspect of the present invention,this component looks for large or small deviations in the reactionscounts for a set of drugs, i.e., comparing drugs to those in their owntherapeutic category or to all drugs. With a preferred embodiment of thepresent invention, a user has an option to compute for a therapeuticcategory using a pull-down menu. A user also has an option of selectingBayesian filtering. Bayesian filtering employs a statistical cut-offthreshold to reduce the affect of rows or columns with a very low numberof cases. That is, drugs or reactions accounting for less than a certainpercent of cases or fewer than a set number will be deleted from thematrix (and so noted on the results screen).

A user preferably has two options in running this analysis: (1) he/shecan compute information for each drug's reactions in comparison with allof the drugs in the system or (2) a user can run an analysis, bycomparing the selected drug's reactions only with those of other drugsin the same therapeutic category. Results are preferably presentedconcurrently on a separate screen.

An additional preferred aspect of this home page is a comparator, whichis available when a user is accessing optionally provided clinical trialdata from a drug label, or from the clinical trial data of an internaldatabase. The comparator compares potential and actual adverse effectsof drugs in the pre- and post-market environments.

The preferred home page of the present invention also provides a userwith the options to add a user, manage preferences, manage the group ofinserts, and to log out, among others.

If a user has selected a query at the Home page, he/she will initiate aquery for a drug using the drug's generic name, its trade name, itstherapeutic category, its chemical name, or other custom-definedcategories. The search invokes the selector page of the presentinvention. A user selects a drug by clicking on the generic drug linkwhich then takes a user to the profile and general statistics regardingthe selected drug. A user starts his/her search on the home screen, andthen continues it on the selector page, by entering or selecting thecategory of drug he/she wants to search: the generic name, the tradename, the therapeutic category or the custom-defined categories. Thetherapeutic category field preferably has a pull-down menu to helpidentify and select the desired field.

An exemplary Query Screen page is illustrated in FIG. 5, where a userhas decided to search the therapeutic category of angiotensin convertingenzyme (ACE) inhibitors, as defined by the drug dictionaries. (Note: Inthis case the FDA taxonomy places certain drugs known as ATII drugs inthe ACE category). Here, the user has chosen not to use the generic namefield 500 or the trade name field 501, but rather has chosen thetherapeutic category field 503. The present system returns with the hitscorresponding to the selected therapeutic category and are displayed inthe query screen. In this example, 4 drugs matching the search criteriawere found in the “ACE Inhibitors” category. The drugs are listed inalphabetical order by their generic name. For each generic drug on thelist, all trade names and all relevant therapeutic categories arepresented in pull-down menus. Optionally, custom-defined categories canalso be shown. The search results also allow access to the drug's“pedigree,” or lexical mapping information, indicated by a question marklink.

Preferably, a user can stop browsing drugs and go directly to theprofile by selecting and applying a previously stored filter.

With regard to the pedigree function, if a user selects the pedigreeicon for the selected drug (the question mark in this example), a useris presented with the drug's pedigree, which shows the way the drug hasbeen mapped in a drug dictionary and thesaurus.

An exemplary pedigree screen is presented in FIG. 6. This exemplarypedigree screen provides a number of preferred fields indicating thecataloging of the data in the system of the present invention. Preferredfields include, but are not limited to, Map To (field 600), Verbatim(field 601), Source (field 602), Incidents (field 603), Case Count(field 604), QEDRx Processing (field 605), Cross-Reference (field 606),and First/Last Reported Reactions (field 607). The data pedigree searchnot only shows how the drug is catalogued in the present invention, italso shows the drug's mapping to known dictionaries. These data aredisplayed in a tabular form, and indicate the logical route fromverbatim terms to the “map to” terms used to search the database. Thisfunction informs the user of specific ranges, types of corruption andnumber of each type of corruption in the data that have been corrected.

For example, a preferred pedigree screen of the present inventionprovides categories including Map to, Verbatim, Cross-Reference,Incidents, Case Counts, QEDRx Processing, First/Last Reported Reactions,and Source. The Map to category shows how the verbatim name was mappedto a generic or trade name. The Verbatim category shows the verbatimname the drug was found under in the database. This can be any form ofthe name under which this drug was found in the FDA database, andincludes misspellings, variations, etc. The Cross-reference categoryindicates which data source contains this verbatim, the SRS database orthe AERS database, etc. The Incidents category indicates the number oftimes this verbatim appears in the database. The QEDRx Processingcategory refers to the “cleanup” performed on the data. The specificprocessing steps are defined in a key. The Source category indicateswhich reference data source was used to map this verbatim to a generic.

The key explains the types of processing that the system and method ofthe present invention performs to standardize drug names and to improvethe quality of the reported data. The present invention preferablyperforms five types of processing: spelling correction (correctsmisspelled drug names and standardizes variations in drug names), noisewords (works like, for example, “tablets” “Prozac tablets” does notoffer further information about the drug itself; it simply providesinformation on how the drug was administered), combo words(alphanumerics like “20 mg.,” for example, which are redundant becausealready in the database), numerics (the “20” in 20 mg. In this case, 20is a numeric and “mg” is a noise word), marks (extraneous typographicalsymbols, such as brackets, dashes, and so forth). Additional aspects ofthis feature of the present invention are provided in U.S. Pat.6,778,994, entitled Pharmacovigilance Database, which is incorporatedherein by reference.

The profiler aspect of the present invention permits a user to navigatevarious dimensions of the selected drug's safety profile and view cases,concomitant drugs, reactions, demographics, outcomes, and time intervalsusing specified filters. Once a user is satisfied with the casesprofiled, the set of cases satisfying the filter criteria can then besubmitted to the various data mining engines, including the CorrelatorEngine (CE), Proportioning Engine (PE) and Differencing Engine (DE).Each data mining engine is provided with a set-up and a verificationstep (by means of a page set of input parameters). For example, the CEmay further weight the different dimensions.

It will also be appreciated that the profiler of this invention allowsfor continuous adjustment and addition to the dimensions. For example, apreferred embodiment includes “Repeat Source”. Others may containlaboratory results. The invention permits expanding and contracting boththe profiler and the at least two filters as the data changes.

As noted above, in the selector component of the present invention, eachof the drugs in the generic name category is preferably presented in aformat that indicates a hyperlink. Clicking on a generic drug (in theprevious example Candesartan Cilexetil), the multi-dimension profilescreen is invoked by clicking on a generic drug (in the previous exampleCandesartan Cilexetil).

The idea of profiling a drug is complex, because of the multipledimensions. The invention's profiler separates presenting data on theselected drug into several different categories and preferably“billboards” the top ten for immediate visibility. It will beappreciated that the user can specify any number for “billboarding.” Atthe top of the screen are the generic name of the drug (preferably witha hyperlink to its pedigree), all the trade names associated with thedrug, and all of the therapeutic categories to which it belongs.

The profile feature of the present invention is used to displaystatistics that describe the effects of the drug in multiple dimensions.Each set of data is preferably presented in a separate table, headed byan index tab. The preferred data sets include, but are not limited to:(1) Reactions; (2) Concomitant Drugs; (3) Demographics; (4) Report Dates(for example, dates logged by FDA as report dates for SRS and AERS); and(5) Outcomes.

For each dimension there are key actions: all allow filtering anddelving for more details. The filter action allows a user to set andactivate filters for that dimension. The “More Detail's” action bringsup all the values that have appeared only in the top 10 billboard styleon the main page.

For certain dimensions, for example reactions, the hierarchy of thedimension can be selected to change the billboard and detailed views. Inthe case of reactions, MedDRA contains a five level hierarchy. Otherdictionaries use two to four levels. The present invention accommodatesthe full range of hierarchies.

Preferably, the profiler feature of the present invention allowsgrouping concomitant drugs by therapeutic category, chemical class, orother custom-defined class.

With regard to the Reactions dimension, the profiler component of thepresent invention preferably shows reactions to the drug that is beingqueried. This dimension refers to suspected adverse reactions to theselected drug that were reported. A suitable reactions table is providedin FIG. 7. In this figure, to the right of the Reactions tab is apull-down menu labeled “View” 700, followed by a filter hyperlink 701.By utilizing the pull down menu, a user can choose among multipledifferent levels of MedDRA. Of these multiple different levels ofMedDRA, four are particularly preferred. These are System, Organ, Class(SOC), High Level Group Term (HGLT), High Level Term (HLT), andPreferred Term (PT).

In FIG. 7, a user has chosen the HLT option. The window in the pull-downmenu indicates that there are 256 HLTs out of the total of 1495 HLTs inthe current version of MedDRA. The Reactions Table 702 shows the Top 10HLTs of the 256. In this case, the reactions include hypertension,disturbances in consciousness, and so forth. For each of the reactions,the table presents the Reaction Count (the number of times this reactionwas listed in the database) and the percentage of reactions that thisnumber constituted in the set of reactions for this drug, based onincidents of reactions (not cases).

At the bottom of the Reaction Count and % of Reactions columns arenumbers showing the number of incidents of the reactions at the Top 10HLTs (488) and the Total Reactions across all of the 256 HLTs (in thiscase, 1752), 703 and 704, respectively.

The ability to browse statistics, up and down a hierarchy, and withinreal time, is important to keeping risk assessment hypothesis settingand testing within a short period of time. The invention providesextensive associative tables and reverse indexing to enable such rapidanalysis.

A hyperlink offering more details concurrently follows the Reactionstable, and brings up a separate page with all details of this dimension.

It will be appreciated that since Reactions, Concomitant Drugs, andOutcomes are summarized at the event level, the resultant collection ofcases will be different if more than one event is associated with asingle case. For example, if two reactions are recorded in a singlecase, and both of those reactions parent to the same MedDRA SOC, thenthey will account for two events, and yet would yield only a single casein the case listing.

In a preferred embodiment of the present invention, case levelpercentages and percentage relative to drug exposure are also availablein the profiler component of the present invention. With regard to theConcomitant Drugs dimension of the profiler of the present invention,this dimension describes drugs that were also prescribed in the cases inwhich the target drug was found. A suitable example of a ConcomitantDrugs table is provided in FIG. 8.

In this figure, the Concomitant Drugs Table 800 lists the top 10 drugsin the concomitant category. In this example, hydrochlorothiazide,aspirin, and furosemide were among the drugs found in combination withCandesartan Cilexetil in the adverse reactions reported to the FDA.

The table divides the cases of concomitant drugs into two groups:Suspect and Non-suspect (fields 801 and 802, respectively). When anadverse reaction report is filed, certain drugs in the case may beindicated as suspect. When considering concomitant drugs, these drugswill be either suspect or not in the cases relating to the queried drug(in this case, Candesartan Cilexetil). Thus, in this example there arefour cases to consider, suspect and non-suspect for the queried drug,and suspect and non-suspect for the concomitant drug.

In the example, Hydrochlorothiazide is the drug found to be mostfrequently interacting with Candesartan Cilexetil. The total number ofincidents (45) is broken out into the Suspect and Non-suspectcategories, and the total is also displayed as a percentage of casesthat mention this concomitant drug (it is assumed a drug is onlymentioned once per case), in this case 10.79% of the total number ofcases involving Candesartan Cilexetil. The remaining Top 10 concomitantdrugs are listed in order of descending frequency.

Because it is difficult to predict the number of drugs that arereported, the drug detail section provides browser paging and sorting.Paging and sorting are techniques of the invention used to “bubble tothe top” the significantly hypothesized items.

Concerning the Demographics dimension of the profiler component, thistable provides demographic information about the population included inthe query. An appropriate demographic table in the profiler of thepresent invention is provided in FIG. 9. Preferably five age groups,ranging from below 16 to above 75, are included in field 900. The datais also preferably broken out by gender (field 901). The category totalsand percentages are also provided. The detailed listing gives thestatistics by single age rather than by generational grouping.

Regarding the Report Dates dimension of the profiler component, reportdates for the incidents included in the selected drug query arepresented. A suitable report dates table is presented in FIG. 10. In theexample, the time interval (field 1000) is the decade 1990-1999 andshows the number of reports in each of those years for the drugCandesartan Cilexetil.

The time interval of the incidents included in this query is presentedin this table. In the example, the time interval is 1990-1999 and showsthe total number of reports for that period (field 1001)(446) and thepercentage (field 1002)(in this case, 100.00%) of reports for the drugCandesartan Cilexetil that fall within that time interval. By selectingthe more details link, a user can obtain the breakdown of the reports byindividual years.

In the Outcomes dimension of the profiler of the present system andmethod, case outcomes are listed. An appropriate outcomes table ispresented in FIG. 11. Preferred categories include serious outcomes suchas congenital anomaly, death, and disability, as well as other outcomes.Serious outcomes are preferably presented in red, while less- ornon-serious outcomes are in black. The Outcomes Table provides a tableof outcomes (field 1100), a count (field 1101) and percentages of theoutcomes (field 1102) in each category, as well as totals of serious andnon-serious outcomes.

The filtering feature of the present invention is a paradigm thatreduces the routine of constructing ad hoc queries. This filteringfeature is context-sensitive and relieves a user of the burden ofrepeatedly defining the parameters of the queries. Filtering allows auser to formulate queries in a way more consistent with paradigms usedby medical professionals, selecting among the active cases and usingstandard dictionaries such as MedDRA and National Drug Code Directory.This filtering features preferably allows a user to apply and viewfilters individually, set filters as a group and apply globally, or saveand apply filters at a later time.

Data is compiled by the filters selected for each analysis. In the aboveexample, filters were established for the reaction query. One of thescreens in the profiler component was the reactions dimension, providingthe Top 10 SOCs for the drug Candesartan Cilexetil. At the top of thetable was a pull-down menu with “View” selected, also provided with afilter hyperlink.

Each of the data sets in the Profiler (Reactions, Concomitant Drugs,Demographics, Report Dates, and Outcomes) provides a user with theopportunity to establish filter parameters in any order. In a preferredimplementation, the invention tabs the individual filters forconvenience, and allows merging with other filters.

An exemplary filter applied as to reactions is provided in FIG. 12. Thisfigure provides the list of Reaction Filters available for profiling.The filter is based on the MedDRA hierarchy and begins at the SOC level.

The mechanics for working with filters is common to all dimensions. Auser may click on any or all of the reactions they would like to haveincluded in the filtered reaction profile.

In the example of Reaction filtering, clicking on an SOC brings up theHLGTs for that SOC and allows selection at that level.

In a preferred embodiment filtering can be done at all levels.

It will be appreciated that for the more complex filters, such as thereaction filter, a range of user friendly aids is provided. Fordisplayed MedDRA leads, preferably a tree is used. When it is collapsed,an open box preferably means no selections lower in the hierarchy havebeen identified, a check means all lower selections in the hierarchyhave been identified, and a new query box is used to indicate uncheckedbox(es) somewhere below in the hierarchy.

Another preferred feature of the present invention is content-basedpre-filters. To make it easier to switch-off indication-related adversedrug reactions, an “indications-related” button is preferably providedin the selection. For labeled adverse effects, of which there could behundreds, the invention preferably provides tables (in this case withdata from drug labels) to switch off all of the labeled reactions. Thisquickly focuses the user's attention on “unexpected” reactions.

Preferably on the profiler component, the present invention monitors thecontents of each filter as it is built. At any point, the filter can besaved as an entirely new filter or by overwriting an old one, orchanging and saving an incremental filter. This permits fine tuning ofhypotheses regarding adverse drug reactions.

The filter for the concomitant drugs dimension allows selecting ordeselecting any and each of the concomitant drugs reported in theprofiled set of cases. Similar to reaction filtering, the concomitantdrug dimension filter preferably provides a context selector (forexample, to switch out a whole therapeutic category).

The demographics filter allows selections of generational or individualage brackets, and male/female selections as well. Generational filtersare preferably user definable.

The report dates dimension allows selection by bracketed years. Inaddition, in another embodiment of the invention, the report datesfilter incorporate a link to a drug's birth date and allow filtering by“first six months,” “first two years,” etc. A table of drug birth datesrelieves the user of the need to separately enter those dates.

The Outcome filter allows individual outcome selection, or byserious/non-serious grouping. For internal database adverse events, if acustom seriousness set is defined, this dimension will be userdefinable.

The analysis provided by the system and method of the present inventionfinds “signals” such as anomalies in a random population, a changeagainst a known background, or a coherent target in a noise background.This is accomplished by at least one of three or more data miningengines: the proportional analysis engine (PE), the comparator(differencing engine or DE), and the correlator. In a preferredembodiment, the proportional analysis engine can be invoked from thehome screen, as can be the comparator, for selected data. The correlatoris invoked after filtering cases from the profile page.

The correlator looks for the association of characteristics in literallymillions of pieces of drug/reaction/demographic informationconcurrently.

Too often in risk assessment, important correlations are hidden bysurrounding background “noise” that obscures connections among dataelements. Using a multidimensional vector analysis, the correlatormeasures the degree of association among pairs of values (for example, adrug and a reaction, an age and an outcome, etc.). The correlationalgorithm is user selectable and definable. The preferred version uses aPearson product-moment correlation known conventionally as “R²”. Otheralgorithms can also be used. The invention preferably applies thecorrelation after filtering, greatly enhancing the signal and reducingnoise.

As a preferred example, the profiler screen can provide a number ofhyperlinks choices, including “Apply Filter” and “Compute Correlations.”selecting “Compute Correlations,” a user initiates the correlatorengine, using the active set of cases, based on the filter in use. Whilethe processing is being carried out, a user is preferably returned tothe home screen, where a message alerts a user that the correlation isbeing executed. Once the analysis is completed, a user is notified thatthe correlation has been completed and providing a user with the optionto view the correlation results.

FIG. 13 provides an exemplary screen presenting the results of acorrelated search. The line listing of correlated terms (which may beseveral screens in length) consists of the top 200 (this cut-off numbercan be any number that the user specifies and is selectable andsortable) sets of correlated terms for a user's analysis on therequested drug. The data compares the correlations between “Term 1” and“Term 2.” For each pair of terms, the screen preferably shows itsrelative rank (field 1303); score (field 1304)(the term-pair'scorrelative value relative to other term-pairs, for example, “Female”and “Candesartan” are more “associated” than any other pair of terms,for example, in the set of cases containing “Female” and “Candesartan,”were relatively highly correlated); the identity of the first term(field 1300) and the category to which it belongs (field 1305); and theidentity of the second term (field 1301) and the category to which itbelongs (field 1306).

Although the product moment correlation has been employed in a number ofareas, it has typically been used for numerical data. The inventionsends the correlator a vector comprising almost entirely of categoricalterms, a new and previously unexplored use of the Pearson R². Thepresent invention's structural database, its ability to keep aconsistent vocabulary (to name categories of a categorical variable) andits ability to provide sufficiently cleaned data regarding adverse drugreactions make the correlation meaningful. The present invention'sability to sort results, compare significance and handle thousands ofcases was not available in the prior art. Since the correlatorcalculates association strength for both known factors (for example, ageand gender) and rare reactions (for example, adverse drug reactions(ADR's)), this invention can identify meaningful relationships nototherwise easily observed.

In addition to viewing the table listing online, a user may alsopreferably select to review the results using a “radar-screen”correlation viewer. On the correlation screen, after the “Below are thetop 200 correlated terms for your analysis . . .,” there is preferably ahyperlink that provides the option of viewing the results with thecorrelation viewer. In addition to viewing with the correlation viewer,a user is also preferably presented with options to save the file.

Two other information screens preferably provide additional informationprovided by the correlation engine. From the correlated terms screen, auser is preferably presented with hyperlinks comprising all of thenumbers in the Rank column. A significance (to a user-selectable “P”value) is also preferably provided. These hyperlinks provide a link toindividual case lists. An exemplary correlation details screen isprovided in FIG. 14.

The Correlation Details screen of FIG. 14 provides the data for each ofthe cases included in that pair of correlated terms. For example, if theterm pair in the Correlated Terms Screen was “Female” and “CandesartanCilexetil,” this screen provides the pertinent information for all ofthe cases where those two terms were paired. In this example, there were18 cases where renal function analyses were correlated with CandesartanCilexetil. For each case, preferably the following information isprovided: the case ID (field 1401); the gender of the patient (field1402); the Manufacturer's Control Code (field 1403); the FDA ReportReceipt Date (field 1404); the patient's age (field 1405); the otherdrugs the patient was taking at the time of the incident(s)(field 1406);the patient's reaction(s) to the medications (field 1407); and whetherthe outcome was Serious (yes or no)(field 1408). By selecting thesecases, the user can then profile the set of cases.

Additionally, to learn the details of a specific case, a user preferablycan click on the case ID number of any case on the Correlation Detailsscreen. The resultant information is preferably presented in a casedetails screen. An suitable case details screen is presented in FIG. 15.

The Case Details screen of FIG. 15 provides detailed information on eachspecific case. In addition to standard information such as the patient'scase ID (field 1501), gender (field 1502), and age (field 1503), itpreferably includes Reactions (field 1504)(including detailedinformation in the As Reported, Preferred Term, High Level Term, andHigh Level Group Term categories); Concomitant Drugs (field 1505)(eachlisted by Name, Dose, Route, and Suspect Status); Outcomes (field 1506);Manufacturer Control Code (field 1507); Manufacturer Date (field 1508);Adverse Event Date (field 1509); Report Type (field 1510); Report Source(field 1511); Case Source (field 1512), and Narrative (field 1513), ifany. All data, including lab test and genetic information can be encodedand displayed.

It will be appreciated that the above-identified information is not theonly information that can be provided; extra information fields may bealso provided.

The adverse effect analysis result of the present invention arepreferably presented in a format that provides both traditional tabulardisplays (line listings) and innovative “radar-like” displays. Bypopulating a radar screen with textual information, a user moves fromthe cumbersome reading of printouts to the instant perception ofcorrelations directly on the screen. Once a signal is identified, a casebrowser permit a user to move through user-defined sorting to the keycases involved. Once again the synergistic aspects of the invention comeinto play. A “Therapeutic Category” or “Labeled Reaction” selector cangroup the data on the radar screen to enhance the signal. An exemplaryradar screen display is presented in FIG. 16.

The proportional analyzer engine of the present invention monitorsoutliers among reactions for drugs, for example, by comparing drugs toall drugs or those in a therapeutic class. The proportional analyzerengine can employ a variety of algorithms, including, but not limitedto, proportion repeating ratio (PRR), ODDS ratio, and proportionalreduction of error (PRE), among others.

The proportional analyzer is preferably invoked from the home screen. Auser is, in a preferred embodiment, prompted to select a therapeuticcategory for analysis by the proportional analyzer engine.Alternatively, a drug or a drug set can be selected. A user can selectthe therapeutic category that contains the drug he/she wishes toanalyze. Bayesian filtering is preferably available as an option toremove noisy results due to lower case counts from the analysis.

In a preferred embodiment of the present invention, a user is promptedas to how he/she would like to analyze the drugs and reactions againstthe reaction counts of all drugs in the system, or only against theirpeers in their therapeutic category. The invention again allowscross-operation of its elements. So, for example, a set of cases can befiltered to use a background for the proportional analysis or a specificcase set can be defined.

Upon completion of the proportional analysis, a proportional analysisscreen preferably presents the results. An exemplary proportionalanalysis screen is presented in FIG. 17. As presented in the figure,this screen preferably has several components, including, but notlimited to a matrix showing the results for the relative ratios; a datablock; and a line listing of the highest 100 relative ratios.

Preferably the proportional analysis screen presents the results of theanalysis as a colored matrix of cells, indicating the frequency ofreactions to various drugs compared to their expected normal frequency.The variation is either more or less frequent than expected, and thecolors of the cells reflect the amount by which the observed number ofreactions differs from the expected amount. Cells that are more darklycolored indicate reaction reporting lower than expected; cells that aregray indicate an as-expected value (or a Relative Ratio (RR) of 1); andcells that are more brightly colored indicate a greater Relative Ratio;the “hotter” the color (yellow to orange to red), the higher thefrequency of reactions.

A user may preferably select any cell in the matrix for furtherinformation. Selecting a specific cell provides details about the drug(field 1800) and its reaction (field 1801), including also the reactioncount (field 1802), the expected reaction count (field 1803), and theRelative Ratio between the two (field 1804). An example of theproportional analysis results screen is provided in FIG. 18.

The invention also allows “analytical drill down”. That is, the abilityto redo the analysis, in a preferred case, for a drug and a reactionsystem-organ-class. The user then selects the level (e.g., PT) forre-analysis and is given the results in real time. The user can theniterate between high level and detail. It will be appreciated that theinvention is not restricted to drug and reaction dimensions forproportional analysis. All pairs of the dimensions of the analyticalengine (for example, reaction and outcomes) can be analyzed. Even withinthe cases of a single drug, the reactions and concomitant drugs could beproportionally analyzed.

In addition to the graphic display, the proportional analyzer also showsthese data in a tabular form. FIG. 19 is the tabular presentation of theproportional analysis results. In this table, the location of the drug(field 1901) and its reaction (field 1900) in the matrix are indicatedby numbers for row and column, row indicating the reaction and columnsignifying the drug of interest. The remaining three columns in thetable preferably indicate the reaction count (field 1902) (with ahyperlink to the cases themselves), the expected reaction count (field1903), and the Relative Ratio (field 1904). The entries are ranked indescending order, with the highest ratios listed first. The columns canpreferably be sorted by clicking on their headings.

As in all tables, from the selector to the correlator, numbers arehyperlinked to the case-list. In the proportional analysis engine, allHLTs are available.

The comparator or differencing engine screen in the preferred offeringoffers three sets of analyzed data: Pre/Post Market data, OtherPost-Market Reaction, and Other Clinical Trial Reaction. An exemplarycomparator screen is provided in FIG. 20. The Pre/Post Market data ispreferably organized into a series of columns in a first table (field2000), providing the information, including Reaction HLT (field 2001);Clinical Trial Reaction (field 2002); Clinical Trial Percentage (field2003), Clinical Trial Adjusted Percentage (field 2004); Post MarketReaction (field 2005); Post Market Percentage (field 2006); Post MarketAdjusted Percentage (field 2007); and Difference Ratio (field 2008). Theadjusted percentages account for proportions of those reactions that arecommon in both pre- and post-market reporting. The second table (field2009) lists Other Post-Market Reaction (field 2010) and each reaction'sPost-Market Percentage (field 2011). This information represents dataavailable in the integrated public database. The third table (field2012)provides Other Clinical Trial Reaction (field 2013)and eachreaction's Clinical Trial Percentage (field 2014). This informationindicates whether this reaction was mentioned on the manufacturer'spackage insert.

The comparator engine of the present invention is a differencing enginethat is applied to measuring one drug's reactions, both pre- andpost-market. This engine is essentially a “proportion of proportions”and is preferably limited to situations where: labeled adverse effectdata can be quantified, terms can be mapped to MedDRA, and a usefulnumber of reports are available for reactions, both pre- andpost-market. The comparator can compare any two sets of cases for anytwo dimensions.

In viewing the results of the system and method of the presentinvention, when a box on a table or in a matrix or a hyperlink isselected, the case listing is generated. When a user clicks on any ofthe numbers, he/she is provided with a listing of each of the casescorresponding to that link. An exemplary Case List is provided in FIG.21. For each case, various information is provided, including case ID(field 2100), gender (field 2101), Manufacturer Control Code (field2102), FDA Report Receipt Date (field 2103), Age (field 2104), Drugs(field 2105), Reactions (field 2106), Seriousness (field 2107)(Y/N ornormal outcome (optional)). These columns can be sorted by clicking ontheir headings. If a user selects a summary view, a profile of the casesin the case list is then calculated and displayed. Additionally, if auser wishes to learn the details of a specific case, he/she can click onthe case ID number of any specific case on the correlation detailsscreen.

This Case Details screen provides detailed information on each specificcase. In addition to standard information such as the patient's case ID,gender, and age, it also includes Reactions (including detailedinformation in the As Reported, Preferred Term, High Level Term, andHigh Level Group Term categories); Concomitant Drugs (each listed byName, Dose, Route, and Suspect Status); Outcomes; Manufacturer ControlCode; Manufacturer Date; Adverse Event Date; Report Type; Report Source;Case Source; and Narrative, if any. As will be appreciated, additionaldetails can be provided. If these details are structured, all featuresof the invention are expandable to that dimension. If the information isunstructured, the invention can extract and structure the data using thedictionary and thesaurus facilities.

It will appreciated that the system and method of the present inventionhas applications in risk assessment other than in the context of drugsafety. For example, the system and method of the present invention canbe used to analyze the causal elements of other events, for example,death or hospitalization, with regard to the other dimensions of theinvention. Additionally, the system and method of the present inventioncan be similarly applied to other problems of signal detection andcorrelation where signals emerge in a large population with manydimensions. In general, the invention is applicable to any situationwhere there are reports (cases), primary elements (drugs, tires), meansfor measuring events (rash, discoloration), outcomes (death, blow out)and unrelated dimensions (age, temperature).

It will further be appreciated that the system and method of the presentinvention has applications in risk assessment in the fields ofdemographics, phenotype, genotype, genomics, and proteomics.Specifically, the system and method of the present invention can be usedassess the risk/susceptibility of an individual or a group of a possibleoutcome (for example, lung cancer, leukemia, Jacob-Kreutzfeld syndrome)based on phenotype, genotype, or environmental exposure. The system andmethod of the present invention permits a user to assess the correlationbetween a possible outcome and multiple dimensions of an individual or agroup.

Various preferred embodiments of the invention have been described infulfillment of the various objects of the invention. It should berecognized that these embodiments are merely illustrative of theprinciples of the invention. Numerous modifications and adaptationsthereof will be readily apparent to those skilled in the art withoutdeparting from the spirit and scope of the present invention.

1-14. (canceled)
 15. A method for assessing and analyzing the risks ofadverse effects resulting from the use of at least one substance ofinterest, comprising: identifying the at least one substance ofinterest; selecting the profile of the at least one substance ofinterest related to the safety of the at least one substance ofinterest, using at least one filter; analyzing the risks of adverseeffects resulting from the use of the at least one substance of interestusing at least one data mining engine; and displaying the results of theanalysis of risks of adverse effects resulting from the use of the atleast one substance of interest.
 16. The method for assessing andanalyzing the risks of adverse effects resulting from the use of atleast one substance of interest according to claim 15, wherein the atleast one data mining engine is a proportional analysis engine to assessdeviations in a set of the reactions to the at least one substance ofinterest.
 17. The method for assessing and analyzing the risks ofadverse effects resulting from the use of at least one substance ofinterest according to claim 15, wherein the at least one data miningengine is a comparator to measure the reactions to the at least onesubstance of interest against a user-defined backdrop.
 18. The methodfor assessing and analyzing the risks of adverse effects resulting fromthe use of at least one substance of interest according to claim 15,wherein the at least one data mining engine is a correlator to look forcorrelated signal characteristics in drug/reaction/demographicinformation.
 19. The method for assessing and analyzing the risks ofadverse effects resulting from the use of at least one substance ofinterest according to claim 15, wherein the data mining engine is atleast two members of the group consisting of a proportional analysisengine, a comparator, and a correlator.
 20. The method for assessing andanalyzing the risks of adverse effects resulting from the use of atleast one substance of interest according to claim 18, wherein the atleast one substance of interest is assessed in combination with otherdrugs, foodstuffs, beverages, nutrients, vitamins, toxins, chemicals,hormones, and supplements.
 21. The method for assessing and analyzingthe risks of adverse effects resulting from the use of at least onesubstance of interest according to claim 18, wherein the method permitsassessment and analysis of the risks of adverse effects resulting fromthe use of at least one drug of interest in any of multiple dimensionsof the risk assessment and analysis. 22-28. (canceled)